Evolution and treatment of vitamin B12 deficiency as a risk factor for (cognitive and functional) neurodegenerative diseases in institutionalized elderly = Evolución y tratamiento de la deficiencia de vitamina B12 como factor de riesgo de enfermedades neurodegenerativas (cognitivas y funcionales) en las personas mayores institucionalizadas.

Prevalence of vitamin B12 deficiency is very common in elderly people and can reach values as high as 40.5% of the population. It can be the result of the interaction among several factors. Vitamin B12 deficiencies have been associated with neurological, cognitive deterioration, haematological abnormalities and cardiovascular diseases that have an important influence on the health of the elderly and their quality of life. It is necessary to approach the problems arisen from the lack of data relative to them. The main objective of this thesis was to analyse the evolution of vitamin B12 status and related parameters, lipid and haematological profiles and their relationship to health risk factors, and to functional and cognitive status over one year and to determine the effect of an oral supplementation of 500 μg of cyanocobalamin for a short period of 28 days. An additional objective was to analyze the possible effects of medicine intakes on vitamin B status. Three studies were performed: a) a one year longitudinal follow-up with four measure points; b) an intervention study providing an oral liquid supplement of 500 μg of cyanocobalamin for a 28 days period; and c) analysis of the possible effect of medication intake on vitamin B status using the ATC classification of medicines. The participants for these studies were recruited from nursing homes for the elderly in the Region of Madrid. Sixty elders (mean age 84 _ 7y, 19 men and 41 women) were recruited for Study I and 64 elders (mean age 82 _ 7y, 24 men and 40 women) for Study II. For Study III, baseline data from the initially recruited participants of the first two studies were used. An informed consent was obtained from all participants or their mentors. The studies were approved by the Ethical Committee of the University of Granada. Blood samples were obtained at each examination date and were analyzed for serum cobalamin, holoTC, serum and RBC folate and total homocysteine according to laboratory standard procedures. The haematological parameters analyzed were haematocrit, haemoglobin and MCV. For the lipid profile TG, total cholesterol, LDL- and HDLcholesterol were analyzed. Anthropometric measures (BMI, skinfolds [triceps and subscapular], waist girth and waist to hip ratio), functional tests (hand grip, arm and leg strength tests, static balance) and MMSE were obtained or administered by trained personal. The vitamin B12 supplement of Study II was administered with breakfast and the medication intake was taken from the residents’ anamnesis. Data were analyzed by parametric and non-parametric statistics depending on the obtained data. Comparisons were done using the appropriate ANOVAs or non-parametric tests. Pearsons’ partial correlations with the variable “time” as control were used to define the association of the analyzed parameters. XIII The results showed that: A) Over one year, in relationship to vitamin B status, serum cobalamin decreased, serum folate and mean corpuscular volumen increased significantly and total homocysteine concentrations were stable. Regarding blood lipid profile, triglycerides increased and HDL-cholesterol decreased significantly. Regarding selected anthropometric measurements, waist circumference increased significantly. No significant changes were observed for the rest of parameters. B) Prevalence of hyperhomocysteinemia was high in the elderly studied, ranging from 60% to 90 % over the year depending on the cut-off used for the classification. LDL-cholesterol values were high, especially among women, and showed a tendency to increase over the year. Results of the balance test showed a deficiency and a tendency to decrease; this indicates that the population studied is at high risk for falls. Lower extremity muscular function was deficient and showed a tendency to decrease. A highly significant relationship was observed between the skinfold of the triceps and blood lipid profile. C) Low cobalamin concentrations correlated significantly with low MMSE scores in the elderly studied. No correlations were observed between vitamin B12 status and functional parameters. D) Regarding vitamin B12 status, holo-transcobalamin seems to be more sensitive for diagnosis; 5-10% of the elderly had a deficiency using serum cobalamin as a criterion, and 45-52% had a deficiency when using serum holotranscobalamin as a criterion. E) 500 μg of cyanocobalamin administered orally during 28 days significantly improved vitamin B12 status and significantly decreased total homocysteine concentrations in institutionalized elderly. No effect of the intervention was observed on functional and cognitive parameters. F) The relative change (%) of improvement of vitamin B12 status was higher when using serum holo-transcobalamin as a criterion than serum cobalamin. G) Antiaenemic drug intake normalized cobalamin, urologic drugs and corticosteroids serum folate, and psychoanaleptics holo-transcobalamin levels. Drugs treating pulmonary obstruction increased total homocysteine concentration significantly. H) The daily mean drug intake was 5.1. Fiftynine percent of the elderly took medication belonging to 5 or more different ATC groups. The most prevalent were psycholeptic (53%), antiacid (53%) and antithrombotic (47%) drugs.

Evaluation of the reliability of commercial concentrator triple-junction solar cells by means of accelerated life tests (ALT)

A temperature accelerated life test on commercial concentrator lattice-matched GaInP/GaInAs/Ge triple-junction solar cells has been carried out. The solar cells have been tested at three different temperatures: 119, 126 and 164 °C and the nominal photo-current condition (820 X) has been emulated by injecting current in darkness. All the solar cells have presented catastrophic failures. The failure distributions at the three tested temperatures have been fitted to an Arrhenius-Weibull model. An Arrhenius activation energy of 1.58 eV was determined from the fit. The main reliability functions and parameters (reliability function, instantaneous failure rate, mean time to failure, warranty time) of these solar cells at the nominal working temperature (80 °C) have been obtained. The warranty time obtained for a failure population of 5 % has been 69 years. Thus, a long-term warranty could be offered for these particular solar cells working at 820 X, 8 hours per day at 80 °C.

Mechanical behavior of tungsten-vanadium-lanthana alloys as function of temperature

The mechanical behavior of three tungsten (W) alloys with vanadium (V) and lanthana (La2O3) additions (W–4%V, W–1%La2O3, W–4%V–1%La2O3) processed by hot isostatic pressing (HIP) have been compared with pure-W to analyze the influence of the dopants. Mechanical characterization was performed by three point bending (TPB) tests in an oxidizing air atmosphere and temperature range between 77 (immersion tests in liquid nitrogen) and 1273 K, through which the fracture toughness, flexural strength, and yield strength as function of temperature were obtained. Results show that the V and La2O3 additions improve the mechanical properties and oxidation behavior, respectively. Furthermore, a synergistic effect of both dopants results in an extraordinary increase of the flexure strength, fracture toughness and resistance to oxidation compared to pure-W, especially at higher temperatures. In addition, a new experimental method was developed to obtain a very small notch tip radius (around 5–7 μm) and much more similar to a crack through the use of a new machined notch. The fracture toughness results were lower than those obtained with traditional machining of the notch, which can be explained with electron microscopy, observations of deformation in the rear part of the notch tip. Finally, scanning electron microscopy (SEM) examination of the microstructure and fracture surfaces was used to determine and analyze the relationship between the macroscopic mechanical properties and the micromechanisms of failure involved, depending on the temperature and the dispersion of the alloy.

Determination of the hoop fracture properties of unirradiated hydrogen-charged nuclear fuel cladding from ring compression tests

In this work, a new methodology is devised to obtain the fracture properties of nuclear fuel cladding in the hoop direction. The proposed method combines ring compression tests and a finite element method that includes a damage model based on cohesive crack theory, applied to unirradiated hydrogen-charged ZIRLOTM nuclear fuel cladding. Samples with hydrogen concentrations from 0 to 2000 ppm were tested at 20 �C. Agreement between the finite element simulations and the experimental results is excellent in all cases. The parameters of the cohesive crack model are obtained from the simulations, with the fracture energy and fracture toughness being calculated in turn. The evolution of fracture toughness in the hoop direction with the hydrogen concentration (up to 2000 ppm) is reported for the first time for ZIRLOTM cladding. Additionally, the fracture micromechanisms are examined as a function of the hydrogen concentration. In the as-received samples, the micromechanism is the nucleation, growth and coalescence of voids, whereas in the samples with 2000 ppm, a combination of cuasicleavage and plastic deformation, along with secondary microcracking is observed.

Mechanical behavior of alkali-cement as function of the temperature.

This investigation reports on a comparative study of the mechanical behavior at different temperatures of three different alkali-activated fly ash pastes chemically activated using sodium silicate. A control Portland cement (OPC) was used as a reference. In an attempt to simulate the conditions prevailing in the event of accidental fire, post-thermal mechanical tests were performed to determine the residual strength. It has therefore been established that FA based cements can be fabricated for construction purposes and these materials have great potential for fire resistance applications.

Evaluation of the reliability of high concentrator GaAs solar cells by means of temperature accelerated aging tests

ABSTRACT Evaluating the reliability, warranty period, and power degradation of high concentration solar cells is crucial to introducing this new technology to the market. The reliability of high concentration GaAs solar cells, as measured in temperature accelerated life tests, is described in this paper. GaAs cells were tested under high thermal accelerated conditions that emulated operation under 700 or 1050 suns over a period exceeding 10 000 h. Progressive power degradation was observed, although no catastrophic failures occurred. An Arrhenius activation energy of 1.02 eV was determined from these tests. The solar cell reliability [R(t)] under working conditions of 65°C was evaluated for different failure limits (1–10% power loss). From this reliability function, the mean time to failure and the warranty time were evaluated. Solar cell temperature appeared to be the primary determinant of reliability and warranty period, with concentration being the secondary determinant. A 30-year warranty for these 1 mm2-sized GaAs cells (manufactured according to a light emitting diode-like approach) may be offered for both cell concentrations (700 and 1050 suns) if the solar cell is operated at a working temperature of 65°C.

Estudio Multimodal de la Funcionalidad Cortical en ratones Transgénicos con Síndrome X Frágil y la modulación del dolor

El dolor es un síntoma frecuente en la práctica médica. En España, un estudio realizado en el año 2000 demostró que cada médico atiende un promedio de 181 pacientes con dolor por mes, la mayoría de ellos con dolor crónico moderado1. Del 7%-8% de la población europea está afectada y hasta el 5% puede ser grave2-3, se estima, que afecta a más de dos millones de españoles4. En la consulta de Atención Primaria, los pacientes con dolor neuropático tienen tasas de depresión mucho mayores 5-6-7. El dolor neuropático8 es el dolor causado por daño o enfermedad que afecta al sistema somato-sensorial, es un problema de salud pública con un alto coste laboral, debido a que existe cierto desconocimiento de sus singularidades, tanto de su diagnóstico como de su tratamiento, que al fallar, el dolor se perpetúa y se hace más rebelde a la hora de tratarlo, en la mayoría de las ocasiones pasa a ser crónico. Los mecanismos fisiopatológicos son evolutivos, se trata de un proceso progresivo e integrado que avanza si no recibe tratamiento, ocasionando graves repercusiones en la calidad de vida de los pacientes afectados9. De acuerdo a Prusiner (premio nobel de medicina 1997), en todas las enfermedades neurodegenerativas hay algún tipo de proceso anormal de la función neuronal. Las enfermedades neurodegenerativas son la consecuencia de anormalidades en el proceso de ciertas proteínas que intervienen en el ciclo celular, por lo tanto da lugar al cúmulo de las mismas en las neuronas o en sus proximidades, disminuyendo o anulando sus funciones, como la enfermedad de Alzheimer y el mismo SXF. La proteína FMRP (Fragile Mental Retardation Protein), esencial para el desarrollo cognitivo normal, ha sido relacionada con la vía piramidal del dolor10-11-12. El Síndrome de X Frágil13-14 (SXF), se debe a la mutación del Gen (FMR-1). Como consecuencia de la mutación, el gen se inactiva y no puede realizar la función de sintetizar la proteína FMRP. Por su incidencia se le considera la primera causa de Deficiencia Mental Hereditaria sólo superada por el Síndrome de Down. La electroencefalografía (EEG) es el registro de la actividad bioeléctrica cerebral que ha traído el desarrollo diario de los estudios clínicos y experimentales para el descubrimiento, diagnóstico y tratamiento de un gran número de anormalidades neurológicas y fisiológicas del cerebro y el resto del sistema nervioso central (SNC) incluyendo el dolor. El objetivo de la presente investigación es por medio de un estudio multimodal, desarrollar nuevas formas de presentación diagnóstica mediante técnicas avanzadas de procesado de señal y de imagen, determinando así los vínculos entre las evaluaciones cognitivas y su correlación anatómica con la modulación al dolor presente en patologías relacionadas con proteína FMRP. Utilizando técnicas biomédicas (funcionalestructural) para su caracterización. Para llevar a cabo esta tarea hemos utilizado el modelo animal de ratón. Nuestros resultados en este estudio multimodal demuestran que hay alteraciones en las vías de dolor en el modelo animal FMR1-KO, en concreto en la modulación encefálica (dolor neuropático), los datos se basan en los resultados del estudio estructural (imagen histología), funcional (EEG) y en pruebas de comportamiento (Laberinto de Barnes). En la Histología se muestra una clara asimetría estructural en el modelo FMR1 KO con respecto al control WT, donde el hemisferio Izquierdo tiene mayor densidad de masa neuronal en KO hembras 56.7%-60.8%, machos 58.3%-61%, en WT hembras 62.7%-62.4%, machos 55%-56.2%, hemisferio derecho-izquierdo respectivamente, esto refleja una correlación entre hemisferios muy baja en los sujetos KO (~50%) con respecto a los control WT (~90%). Se encontró correlación significativa entre las pruebas de memoria a largo plazo con respecto a la asimetría hemisférica (r = -0.48, corregido <0,05). En el estudio de comportamiento también hay diferencias, los sujetos WT tuvieron 22% un de rendimiento en la memoria a largo plazo, mientras que en los machos hay deterioro de memoria de un 28% que se corresponden con la patología en humanos. En los resultados de EEG estudiados en el hemisferio izquierdo, en el área de la corteza insular, encuentran que la latencia de la respuesta al potencial evocado es menor (22vs32 15vs96seg), la intensidad de la señal es mayor para los sujetos experimentales FMR1 KO frente a los sujetos control, esto es muy significativo dados los resultados en la histología (140vs129 145vs142 mv). Este estudio multimodal corrobora que las manifestaciones clínicas del SXF son variables dependientes de la edad y el sexo. Hemos podido corroborar en el modelo animal que en la etapa de adulto, los varones con SXF comienzan a desarrollar problemas en el desempeño de tareas que requieren la puesta en marcha de la función ejecutiva central de la memoria de trabajo (almacenamiento temporal). En el análisis del comportamiento es difícil llegar a una conclusión objetiva, se necesitan más estudios en diferentes etapas de la vida corroborados con resultados histológicos. Los avances logrados en los últimos años en su estudio han sido muy positivos, de tal modo que se están abriendo nuevas vías de investigación en un conjunto de procesos que representan un gran desafío a problemas médicos, asistenciales, sociales y económicos a los que se enfrentan los principales países desarrollados, con un aumento masivo de las expectativas de vida y de calidad. Las herramientas utilizadas en el campo de las neurociencias nos ofrecen grandes posibilidades para el desarrollo de estrategias que permitan ser utilizadas en el área de la educación, investigación y desarrollo. La genética determina la estructura del cerebro y nuestra investigación comprueba que la ausencia de FMRP también podría estar implicada en la modulación del dolor como parte de su expresión patológica siendo el modelo animal un punto importante en la investigación científica fundamental para entender el desarrollo de anormalidades en el cerebro. ABSTRACT Pain is a common symptom in medical practice. In Spain, a study conducted in 2000 each medical professional treats an average of 181 patients with pain per month, most of them with chronic moderate pain. 7% -8% of the European population is affected and up to 5% can be serious, it is estimated to affect more than two million people in Spain. In Primary Care, patients with neuropathic pain have much higher rates of depression. Neuropathic pain is caused by damage or disease affecting the somatosensory system, is a public health problem with high labor costs, there are relatively unfamiliar with the peculiarities in diagnosis and treatment, failing that, the pain is perpetuated and becomes rebellious to treat, in most cases becomes chronic. The pathophysiological mechanisms are evolutionary, its a progressive, if untreated, causing severe impact on the quality of life of affected patients. According to Prusiner (Nobel Prize for Medicine 1997), all neurodegenerative diseases there is some abnormal process of neuronal function. Neurodegenerative diseases are the result of abnormalities in the process of certain proteins involved in the cell cycle, reducing or canceling its features such as Alzheimer's disease and FXS. FMRP (Fragile Mental Retardation Protein), is essential for normal cognitive development, and has been linked to the pyramidal tract pain. Fragile X Syndrome (FXS), is due to mutation of the gene (FMR-1). As a consequence of the mutation, the gene is inactivated and can not perform the function of FMRP synthesize. For its incidence is considered the leading cause of Mental Deficiency Hereditary second only to Down Syndrome. Electroencephalography (EEG) is the recording of bioelectrical brain activity, is a advancement of clinical and experimental studies for the detection, diagnosis and treatment of many neurological and physiological abnormalities of the brain and the central nervous system, including pain. The objective of this research is a multimodal study, is the development of new forms of presentation using advanced diagnostic techniques of signal processing and image, to determine the links between cognitive evaluations and anatomic correlation with pain modulation to this protein FMRP-related pathologies. To accomplish this task have used the mouse model. Our results in this study show alterations in multimodal pain pathways in FMR1-KO in brain modulation (neuropathic pain), the data are based on the results of the structural study (histology image), functional (EEG) testing and behavior (Barnes maze). Histology In structural asymmetry shown in FMR1 KO model versus WT control, the left hemisphere is greater density of neuronal mass (KO females 56.7% -60.8%, 58.3% -61% males, females 62.7% -62.4 WT %, males 55% -56.2%), respectively right-left hemisphere, this reflects a very low correlation between hemispheres in KO (~ 50%) subjects compared to WT (~ 90%) control. Significant correlation was found between tests of long-term memory with respect to hemispheric asymmetry (r = -0.48, corrected <0.05). In the memory test there are differences too, the WT subjects had 22% yield in long-term memory, in males there memory impairment 28% corresponding to the condition in humans. The results of EEG studied in the left hemisphere, in insular cortex area, we found that the latency of the response evoked potential is lower (22vs32 15vs96seg), the signal strength is higher for the experimental subjects versus FMR1 KO control subjects, this is very significant given the results on histology (140vs129 145vs142 mv). This multimodal study confirms that the clinical manifestations of FXS are dependent variables of age and sex. We have been able to corroborate in the animal model in the adult stage, males with FXS begin developing problems in the performance of tasks that require the implementation of the central executive function of working memory (temporary storage). In behavior analysis is difficult to reach an objective conclusion, more studies are needed in different life stages corroborated with histologic findings. Advances in recent years were very positive, being opened new lines of research that represent a great challenge to physicians, health care, social and economic problems facing the major developed countries, with a massive increase in life expectancy and quality. The tools used in the field of neuroscience offer us great opportunities for the development of strategies to be used in the area of education, research and development. Genetics determines the structure of the brain and our research found that the absence of FMRP might also be involved in the modulation of pain as part of their pathological expression being an important animal model in basic scientific research to understand the development of abnormalities in brain.

Mechanical characterisation of tungsten-1wt.% yttrium oxide as a function of temperature and atmosphere

This study evaluates the mechanical behaviour of an Y2O3-dispersed tungsten (W) alloy and compares it to a pure W reference material. Both materials were processed via mechanical alloying (MA) and subsequent hot isostatic pressing (HIP). We performed non-standard three-point bending (TPB) tests in both an oxidising atmosphere and vacuum across a temperature range from 77 K, obtained via immersion in liquid nitrogen, to 1473 K to determine the mechanical strength, yield strength and fracture toughness. This research aims to evaluate how the mechanical behaviour of the alloy is affected by oxides formed within the material at high temperatures, primarily from 873 K, when the materials undergo a massive thermal degradation. The results indicate that the alloy is brittle to a high temperature (1473 K) under both atmospheres and that the mechanical properties degrade significantly above 873 K. We also used Vickers microhardness tests and the dynamic modulus by impulse excitation technique (IET) to determine the elastic modulus at room temperature. Moreover, we performed nanoindentation tests to determine the effect of size on the hardness and elastic modulus; however, no significant differences were found. Additionally, we calculated the relative density of the samples to assess the porosity of the alloy. Finally, we analysed the microstructure and fracture surfaces of the tested materials via field emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM). In this way, the relationship between the macroscopic mechanical properties and micromechanisms of failure could be determined based on the temperature and oxides formed

Mechanical behavior and deformation micromechanisms of polypropylene nonwoven fabrics as a function of temperature and strain rate

The mechanical behavior and the deformation and failure micromechanisms of a thermally-bonded polypropylene nonwoven fabric were studied as a function of temperature and strain rate. Mechanical tests were carried out from 248 K (below the glass transition temperature) up to 383 K at strain rates in the range ≈10−3 s−1 to 10−1 s−1. In addition, individual fibers extracted from the nonwoven fabric were tested under the same conditions. Micromechanisms of deformation and failure at the fiber level were ascertained by means of mechanical tests within the scanning electron microscope while the strain distribution at the macroscopic level upon loading was determined by means of digital image correlation. It was found that the nonwoven behavior was mainly controlled by the properties of the fibers and of the interfiber bonds. Fiber properties determined the nonlinear behavior before the peak load while the interfiber bonds controlled the localization of damage after the peak load. The influence of these properties on the strength, ductility and energy absorbed during deformation is discussed from the experimental observations.